P621: REAL-WORLD DOSING PATTERNS AND TIME TO NEXT TREATMENT FOR PREVIOUSLY UNTREATED PATIENTS WITH CLL/SLL WITH OR WITHOUT IBRUTINIB DOSE REDUCTION FOLLOWING AN ADVERSE EVENT
Authors: Mazyar Shadman, Bhavini Srivastava, Sima Patel, Chadi Saifan, Monika Salkar, Bruno Emond, Priyanka Gogna, Ameur Manceur, Marie-Helene Lafeuille, Deborah Stephens
Journal: HemaSphere (2023)

Background: Ibrutinib, a once-daily oral Bruton's tyrosine kinase inhibitor, is the only targeted therapy to demonstrate significant progression-free survival and overall survival benefit in multiple phase 3 studies for chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). Efficacy outcomes for ibrutinib have been shown to be similar for patients (pts) with a dose reduction (DR) due to adverse events (AEs) compared with pts with no DR (Woyach et al., Cancers 2023). However, real-world data on ibrutinib dosing patterns and the association between DR and outcomes remains scarce. Aims: This real-world study aimed to describe dosing patterns and compare time to next treatment (TTNT) between pts with CLL/SLL with and without DR who were receiving first-line (1L) ibrutinib. Methods: Adults with CLL/SLL who initiated 1L single-agent ibrutinib at 420 mg on or after 2/12/2014 were identified using insurance claims (2/12/2013-12/31/2021) from Optum's de-identified Clinformatics® Data Mart US Database. All pts were required to have an AE during treatment (for each pt, the occurrence of the first incident AE was used as the index date) and ≥90 days of follow-up post-ibrutinib initiation (with no other antineoplastic agents received during this period, to confirm single-agent use). Ibrutinib DR was defined as a reduction from the starting dose of 420 mg following the first incident AE; pts with a DR in the absence of any AE and pts with a DR prior to any AE were excluded from the analysis. Of note, causal association between AE and subsequent DR cannot be inferred from the claims database due to the cross-sectional nature of this study. Pts without a DR were defined as those who remained on 420 mg for the entire duration of 1L therapy. Pts who discontinued ibrutinib treatment were included in both populations (with and without DR). TTNT was defined as time from first incident AE to either first dose of a subsequent treatment or death and was compared between pts with and without DR using a time-varying Cox proportional hazards model adjusted for baseline and time-varying covariates. Results: Among 658 pts treated with 1L single-agent ibrutinib, 95 (14.4%) had a DR (mean age=73.9 years; 40.0% female) and 563 (85.6%) did not have a DR (mean age=72.1 years; 36.6% female) following an AE. Among pts with a DR, the mean (median) duration of 1L therapy was 922 (842) days; the mean (median) time to the first incident AE was 161 (51) days and 760 (725) days between first incident AE and the end of 1L therapy. Among pts with no DR, the mean (median) duration of 1L therapy was 735 (606) days; the mean (median) time to the first incident AE of 227 was (119) days and 508 (352) days between first incident AE and end of 1L therapy. Fewer pts with than without DR had a next treatment or died (30.5% and 39.1%, respectively) and median TTNT was longer among those with vs without DR (59.5 months vs 30.6 months; unadjusted hazard ratio [HR]=0.56, P=0.003; Figure 1). After adjusting for baseline and time-varying covariates, pts with a DR were 38% less likely to have a next treatment or die (adjusted HR=0.62, P=0.017), compared with pts with no DR. Similar results were found for the subgroups of ps with cardiac and non-cardiac AEs. Summary/Conclusion: In this real-world analysis of pts with CLL/SLL treated with 1L single-agent ibrutinib, pts with a DR following an AE had longer TTNT relative to those with no DR. Using TTNT as a marker for disease progression, these findings suggest that ibrutinib DR can be an effective strategy to manage AEs while delaying disease progression.Keywords: ibrutinib, Adverse reaction, Dose intensity, Chronic lymphocytic leukemia